The present invention relates to antiulcer agents and, in particular, to a series of quaternary 8-(alkyldithio)-1-(2-pyrimidyl)quinolinium salts which are inhibitors of the H.sup.+ /K.sup.+ ATPase enzyme. The present invention also includes a method for treating peptic ulcers in mammals, including man; and a composition containing the therapeutic agents of this invention.
Chronic gastric and duodenal ulcers, together known as peptic ulcers, are a common ailment for which a variety of treatments, including dietary measures, drug therapy and surgery, are employed, depending on the severity of the condition. Particularly valuable therapeutic agents useful for the treatment of gastric hyperacidity and peptic ulcers are the histamine-H.sub.2 receptor antagonists, which act to block the action of the physiologically active compound histamine at the H.sub.2 -receptor sites in the animal body and to thereby inhibit the secretion of gastric acid.
Various 2-(pyridylmethylsulfinyl)benzimidazoles, such as omeprazole, and related compounds (Drugs, 32, 15 (1986) are known to be antiulcer agents, acting by a mechanism involving inhibition of the H.sup.+ /K.sup.+ ATPase enzyme system. More recently, such compounds have been reacted with alkyl mercaptans in the presence of an acid to form quaternary 2-(alkyldithio)-1-(2-benzimidazolyl)pyridinium salts, also found to be antiulcer agents with acid suppressing and cytoprotection properties; EP-214,479A. In addition, 8-(2-benzimidazolylsulfinylalkyl)-1,2-dihydro quinoline derivatives are reported in EP application 239,129A to possess such activity.
My copending U.S. patent application Ser. No. 07/156,371, filed Feb. 16, 1988, now U.S. Pat. No. 4,808,591, discloses antiulcer 8-(2-pyrimidylsulfinyl)quinolines. The preparation of these compounds, which are employed as starting materials in the preparation of the compounds of the present invention, is fully disclosed in Preparations herein below.